Hydrogen sulfide pathway and skeletal muscle: an introductory review

Abstract

The presence of the H₂ S pathway in skeletal muscle (SKM) has recently been established. SKM expresses the three constitutive H₂ S-generating enzymes in animals and humans, and it actively produces H₂ S. The main, recognized molecular targets of H₂ S, that is, potassium channels and PDEs, have been evaluated in SKM physiology in order to hypothesize a role for H₂ S signalling. SKM dysfunctions, including muscular dystrophy and malignant hyperthermia, have also been evaluated as conditions in which the H₂ S and transsulfuration pathways have been suggested to be involved. The intrinsic complexity of the molecular mechanisms involved in excitation-contraction (E-C) coupling together with the scarcity of preclinical models of SKM-related disorders have hampered any advances in the knowledge of SKM function. Here, we have addressed the role of the H₂ S pathway in E-C coupling and the relative importance of cystathionine β-synthase, cistathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase in SKM diseases.

Figure 1

Simplified scheme of transsulfuration pathway. The mammalians introduce the aminoacid methionine with the diet. The methionine could be converted into homocysteine and back to methionine. Homocysteine acts as a substrate leading to the synthesis of three major final products: H₂S, taurine and glutathione. http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=279#1446, cysteine aminotransferase; CDO cysteine dioxygenase; CSAD, cysteine sulfonic acid decarboxylase; CSE, cystathionine γ‐lyase; HDD, hypotaurine dyhydrogenase; MPST, 3‐mercaptopyruvate sulfur transferase; MTHFR, methylenetetrahydrofolate reductase.

Figure 2

Potential targets of hydrogen sulfide (H₂S) in SKM. Different recognized, molecular targets of H₂S that are expressed physiologically in SKM: ATP‐sensitive potassium (K_ATP) and voltage dependent (K_V7) channels. Several PDEs that are potential targets for H₂S are also reported. Solid line: activation; dotted line: inhibition.